Genomic profiling proves metastasis of cutaneous melanoma to vitreal fluid.

Cutaneous melanoma metastases can contribute to visual disturbances through a variety of factors, including metastasis to the vitreal fluid. The optimum management of metastatic cutaneous melanoma to the vitreal fluid is unknown, but can include radiation therapy or systemic therapy including immunotherapy. A high degree of suspicion is necessary to consider this complication while working with patients with cutaneous melanoma.

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 µg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.

Is Intravenous Thrombolysis Safe and Effective in Central Retinal Artery Occlusion? A Critically Appraised Topic.

BACKGROUND: Central retinal artery occlusion (CRAO) is a neurological and ophthalmologic emergency associated with poor visual recovery. There is a dilemma regarding the appropriate treatment, as formal guidelines are lacking. Despite being considered an ocular equivalent of cerebral infarction, the time window of intravenous (IV) thrombolysis administration for maximum efficacy and safety in CRAO remains uncertain. OBJECTIVE: To critically assess the current evidence regarding the safety and effectiveness of IV thrombolysis in the treatment of patients with CRAO. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of vascular neurology and ophthalmology. RESULTS: A recent patient-level meta-analysis was selected for critical appraisal. The study compared the visual recovery rates after IV thrombolysis in CRAO against the natural history of this illness and conservative therapies (ocular massage, anterior chamber paracentesis, and/or hemodilution). Time to thrombolytic therapy administration had a significant impact on visual recovery in CRAO (P<0.001). IV thrombolysis within the first 4.5 hours after symptom onset resulted in recovery of vision in 50.0% of the patients [95% confidence interval (CI), 32.4%-67.6%]. The rate of visual recovery was nearly 3 times higher than in the natural history cohort [odds ratio, 4.7 (95% CI, 2.3-9.6); P<0.001], with a 32.3% absolute risk reduction and a number needed to treat of 4.0 (95% CI, 2.6-6.6). There was no significant difference in the recovery rate after thrombolysis compared with the natural history cohort for those patients treated after 4.5 hours. No major hemorrhages occurred after alteplase administration in this meta-analysis. CONCLUSIONS: IV thrombolysis in CRAO seems to be safe and effective within the first 4.5 hours of symptom onset. A clinical decision based on this meta-analysis alone cannot be made due to several limitations. A randomized controlled clinical trial of early IV alteplase administration in CRAO is necessary to provide evidence-based therapeutic guidance.

The diagnostic value of exfoliative cytology vs histopathology for ocular surface squamous neoplasia.

PURPOSE: To determine the reliability and role of conjunctival exfoliative cytologic and histopathologic diagnosis of biopsied tissue in ocular surface squamous neoplasia. DESIGN: Retrospective review of an interventional case series of patients biopsied and treated for squamous conjunctival and corneal neoplasia. METHODS: Forty-nine patients who underwent conjunctival cytologic analysis (n = 36), conjunctival biopsy (n = 35), or both were evaluated. For the purposes of this study, three ocular pathologists reviewed the results of cytologic and biopsied tissue in a masked fashion. RESULTS: Evaluation of cytologic smears revealed a 91% concordance in interpretation of conjunctival cytologic material as no dysplasia vs dysplasia. The concordance dropped to 59% in grading the degree of dysplasia. The cytologic material was found to be inadequate for interpretation in 1 case. Evaluation of subsequent biopsy revealed a 98% concordance between the pathologists in interpretation of biopsied tissue as no dysplasia vs any degree of dysplasia. The concordance decreased to 83% in grading the degree of dysplasia. Cytologic evaluation was capable of distinguishing a neoplastic from nonneoplastic process before tissue biopsy in 80% of cases. CONCLUSIONS: Ocular surface cytologic analysis is a simple, safe, and relatively noninvasive diagnostic tool. It was found helpful in detecting dysplasia before surgical resection. It was used in the settings of recurrent tumor and for follow-up care of patients treated with topical chemotherapy. Although cytologic smears cannot replace incisional or excisional biopsy for definitive diagnosis, exfoliative cytologic analysis can play an important role in the diagnosis and management of patients with ocular surface squamous neoplasia.

Second cancers discovered by (18)FDG PET/CT imaging for choroidal melanoma.

BACKGROUND: Positron-emission tomography/computed tomography (PET/CT) is a unique imaging tool that aids in the detection of cancerous lesions. It is currently and widely used for cancer staging (both initial and follow-up). Here we report our findings of second primary cancers incidentally discovered during PET/CT staging of patients with choroidal melanomas. METHODS: We performed a retrospective case review of 139 patients with uveal melanoma who were subsequently evaluated by whole-body [18-fluorine-labeled] 2-deoxy-2-fluoro-D-glucose ((18)FDG) PET/CT imaging. In this series, 93 were scanned before treatment and 46 during the course of their follow-up systemic examinations. Their mean follow-up was 50.9 months. RESULTS: Six patients (4.3%) had second primary cancers revealed by PET/CT imaging. Three patients (50%) were synchronous (found at initial staging), and the remaining 3 patients (50%) were metachronous (found at follow-up staging). Second primary cancers were found in the lung, breast, uterus, colon, and thyroid. CONCLUSIONS: Although whole-body PET/CT scans were ordered as part of the staging process of patients with diagnosed choroidal melanoma, both synchronous and metachronous second primary cancers were found. PET/CT has become an indispensable tool for staging, diagnosis, and treatment planning for choroidal melanoma. The possibility of detecting second primary cancers should also be considered valuable.

Conjunctival malignant melanoma-associated pseudomelanoma of the apposing tarsal conjunctiva.

PURPOSE: To describe a case of conjunctival malignant melanoma associated with pseudomelanomatous alteration of the apposing tarsal conjunctiva. METHODS: A 93-year-old woman presented with an elevated, pigmented mass on her superior bulbar conjunctiva. The tumor was associated with increased pigmentation of the apposing superior tarsal conjunctiva. An excisional biopsy of the epibulbar melanoma and pigmented tarsal conjunctiva was performed. RESULTS: Histopathologic evaluation of the epibulbar tumor revealed epithelioid melanocytes diagnostic of malignant melanoma. Histopathologic evaluation of the pigmented tarsal lesion showed large areas of ulceration and foci of granulation tissue composed of neovascular sprouts arising in the background of a loose connective tissue, with a moderate chronic inflammatory infiltrate. The infiltrate was composed of mature lymphocytes, plasma cells, and scattered histiocytes. Densely packed intracytoplasmic, brown pigment granules that stained positive with HMB 45 were found, attesting to adjacent melanocytes' releasing melanin-laden granules. There was no evidence of malignancy in the pigmented tarsal specimen. CONCLUSION: Noncontiguous pigmented conjunctival tumor can be found in apposition to an epibulbar melanoma. Although a limited biopsy could be considered, only a complete resection and histopathologic evaluation can determine whether the entire lesion is free of malignant melanoma.

Whole-body positron emission tomography/computed tomography imaging and staging of orbital lymphoma.

OBJECTIVES: To report the use of whole-body positron emission tomography fused with computed tomography (PET/CT) for the diagnosis and staging of orbital lymphoma. DESIGN: Retrospective observational case series. PARTICIPANTS: Four patients with biopsy-proven orbital lymphoma were evaluated by 18-fluoro-2-deoxyglucose whole-body PET/CT imaging. METHODS: Positron emission tomography/CT images were studied for the presence of glucose uptake. Foci were considered suspicious based on their standardized uptake values (SUVs). Physiologic images (PET) and their anatomic counterparts (CT) were fused to allow form and function to be evaluated on the same diagnostic page. MAIN OUTCOME MEASURES: Positron emission tomography/CT images were assessed for foci with abnormally high SUVs that correlated with biopsy-proven lymphoma. RESULTS: Positron emission tomography/CT detected orbital lymphoma in 3 patients (75%). It also revealed systemic lymphoma in 2 of the 4 patients. The 2 patients found to have systemic lymphoma were diagnosed to have extranodal marginal zone B-cell orbital lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Similarly, the 2 with negative PET/CT results also had orbital MALT-type lymphoma. We found that PET/CT imaging helped guide further management in all 4 patients. CONCLUSIONS: Positron emission tomography/CT should be considered as a new method of diagnosing, staging, and restaging patients with orbital lymphomas.

Eyelid-sparing adjuvant radiation therapy for renal cell carcinoma.

PURPOSE: To describe the use of debulking surgery with adjuvant external beam irradiation as an eyelid-sparing treatment for renal cell carcinoma. DESIGN: Interventional case report. METHODS: A 63-year-old male presented with a right upper lid tumor. He had a history of renal cell carcinoma and pulmonary metastasis treated with surgery and systemic chemotherapy. The eyelid tumor was biopsied, followed by debulking surgery and external beam radiation therapy to treat this metastatic tumor. RESULTS: Histopathological evaluation of the excised tumor revealed a metastatic renal cell carcinoma, clear cell type. At 4 months' follow-up, he had no evidence of recurrence or radiation oculopathy. He was pleased with his cosmetic result. CONCLUSIONS: Meta static renal cell carcinoma presenting in the eye and orbit can be the initial manifestation of the primary tumor. It is important to include this tumor in the differential diagnosis of recurrent eyelid lesions. Debulking surgery followed by external beam radiation therapy can be used to control the tumor with an eyelid-sparing cosmetic result.

Peribulbar oncocytoma: high-frequency ultrasound with histopathologic correlation.

The clinical, ultrasonographic, and histopathologic characteristics of an oncocytoma of the conjunctiva are described. A 49-year-old woman presented with a red-orange lesion adjacent to the caruncle in her left eye. A clinical examination including high-frequency ultrasound was performed prior to excisional biopsy of her tumor. High-frequency ultrasound demonstrated an epibulbar tumor with low internal reflectivity and a cystic component. There was no involvement of the underlying sclera. Multiple hypoechoic components of the tumor stroma were correlated to multiple cystic glandular structures on histopathologic evaluation. The excised tumor was diagnosed to be an oncocytoma.

Giant secondary conjunctival inclusion cysts: a late complication of strabismus surgery.

PURPOSE: To present giant conjunctival inclusion cysts as a late complication of strabismus surgery. DESIGN: Retrospective case series of selected patients. PARTICIPANTS: Four patients with a history of strabismus surgery who had developed giant conjunctival inclusion cysts. METHODS: A chart review was performed. The patient's ocular history, ophthalmic examinations, and imaging (ultrasound/ultrasound biomicroscopy and/or computed tomography) were recorded. Surgical excision with subsequent histopathologic correlation was obtained in 3 cases. MAIN OUTCOME MEASURES: Clinical and imaging characteristics with histopathologic correlation. RESULTS: Four patients with giant conjunctival inclusion cysts had a history of strabismus surgery. Ultrasound biomicroscopy was performed in 3 cases and revealed large, cystic, well-circumscribed tumors with low internal reflectivity and hyperechoic components. Computed tomography of the orbits was used to evaluate posterior extension. Their size induced limitation in motility, strabismus, and problems related to chronic exposure. Histopathologic evaluations were consistent with benign inclusion cysts of the conjunctiva. CONCLUSIONS: Giant conjunctival inclusion cysts may appear decades after strabismus surgery. Tumor size, cystic nature, and involvement of underlying structures can be determined by ultrasonography and radiographic imaging. Complete surgical removal can be curative.

The kidney, cancer, and the eye: current concepts.

Herein, we review the associations between the kidney, renal cancers, and the eye. Renal cancers have been reported to metastasize to the eye and the orbit. As these tumors can be confused with other amelanotic or vascular tumors, a high index of suspicion is required for early detection and management of the primary tumor. We discuss the physiology of metastases, clinical features and management of metastatic disease. A variety of ocular anomalies have been associated with renal disease. Wilms tumor, a renal tumor of childhood, can present with aniridia, which may be the first clue leading to the diagnosis of the primary tumor. Paraneoplastic syndromes are common manifestations of renal cancers and can present as retinopathies and neuro-ophthalmic disorders. Multiple cancer syndromes involve both the eye and the kidney. For example, the diagnosis of von Hippel retinal tumors can lead to a systemic evaluation and discovery of associated visceral tumors. The prognosis, screening, and counseling of such patients is discussed. Newer systemic treatments available for renal tumors, such as interferon alfa, may lead to ocular side effects including retinopathy. These patients require periodic ophthalmic examinations. This review demonstrates the essential role of the ophthalmologist, for early diagnosis and treatment that can help reduce the morbidity and mortality associated with kidney tumors and renal-associated disease.

Whole body positron emission tomography/computed tomography staging of metastatic choroidal melanoma.

PURPOSE: To evaluate whole-body positron emission tomography (PET)/computed tomography in staging of patients with metastatic choroidal melanoma. DESIGN: Interventional non-randomized clinical study. METHODS: Twenty patients were referred for whole-body 18-fluoro-2-deoxy-D-glucose (FDG) PET/computed tomography imaging because of suspected metastatic choroidal melanoma. PET/computed tomography images were studied for the presence and distribution of metastatic melanoma. Subsequent biopsies were performed to confirm the presence of metastatic disease. RESULTS: Twenty patients underwent PET/computed tomography. Eighteen were imaged because of abnormal clinical, hematologic, or radiographic screening studies during the course of their follow-up after plaque brachytherapy or enucleation. Two were imaged before treatment of their primary tumor. PET/computed tomography revealed or confirmed metastatic melanoma in eight (40%) of these 20 patients. The mean time from initial diagnosis to metastasis was 47 months (range 0 to 154). The most common sites for metastases were the liver (100%), bone (50%), lung (25%), lymph nodes (25%), and subcutaneous tissue (25%). Cardiac, brain, thyroid, and posterior abdominal wall lesions (12.5%) were also noted. Six patients (75%) had multiple organ involvement. No false positives were noted. PET/computed tomography imaging also detected benign lesions of the bone and lymph nodes in three patients (15%). All patients had hepatic metastases and liver enzyme assays were abnormal in only one (12.5%) of eight patients. CONCLUSIONS: PET/computed tomography imaging is a sensitive tool for the detection and localization of hepatic and extra-hepatic (particularly osseous) metastatic choroidal melanoma.

Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years' experience.

PURPOSE: To report 12-year follow-up experience with topical mitomycin chemotherapy for diffuse and multifocal primary acquired melanosis (PAM) with atypia and conjunctival melanoma. METHODS: Interventional case series of 16 patients. Mitomycin was a primary treatment for residual epithelial disease in ten patients (eight with PAM with atypia and two with conjunctival melanoma) and as an adjuvant to excision and cryotherapy in six with conjunctival malignant melanoma. Primary treatments consisted of mitomycin 0.04% qid for 28 days (two 14-day cycles) and for 7 consecutive days as adjuvant therapy. Patients were followed for both local recurrence and metastatic disease. RESULTS: Sixteen patients were followed for a mean 81 months (range 13-144 months) after treatment. All tumors responded to chemotherapy. Recurrence was noted in eight (three adjuvant and five primary treatment patients). Three underwent orbital exenteration. The remaining five were treated conservatively. The mean time to recurrence was 36.9 months. The short-term mitomycin-related complications included transient keratoconjunctivitis (n=14), severe keratoconjunctivitis (n=1) and one corneal abrasion with scar formation. The long-term complications included pannus (n=2) and corneal haze (n=1). Visual acuity was maintained within two lines in 14 patients (including measurements just prior to exenteration). Three patients died, one of metastatic conjunctival melanoma. CONCLUSIONS: Conjunctival melanoma and PAM responded to mitomycin 0.04% topical chemotherapy; subepithelial nests appeared resistant to treatment. Treatment-related complications were acceptable. In this series, as primary and adjuvant therapy, topical mitomycin yielded an overall recurrence rate of 50%.

Melanocytic conjunctival tumors.

Melanocytic conjunctival tumors include a wide range of lesions that vary in their clinical and histopathologic features. Their management depends on numerous factors, including their location, focality, tumor dimensions (including depth), histopathologic characteristics, recurrences, growth, and the presence of metastasis.

Visual recovery after radiation therapy for bilateral subfoveal acute myelogenous leukemia (AML).

PURPOSE: Present a case of bilateral foveal acute myelogenous leukemic tumors that responded to radiation therapy. DESIGN: Case report. METHODS: A patient was diagnosed with bilateral subfoveal infiltration of known systemic acute myelogenous leukemia. He received a standard induction chemotherapy, followed by consolidation therapy for his systemic leukemia. However, despite a complete marrow response, the intraocular tumors did not regress. Therefore, he was given low dose (1950-cGy) ocular external beam radiation therapy. RESULTS: One course of systemic cytarabine chemotherapy failed to control the subfoveal tumors, leaving the patient at risk for permanent vision loss. In contrast, external beam radiation therapy improved his vision from 20/60 in his right eye to 20/20 and from 20/70 in his left eye to 20/25. CONCLUSION: Although systemic chemotherapy can be used to treat intraocular metastasis, external beam radiation may provide more prompt resolution of vision-threatening tumors.